title: PrLZ protects prostate cancer cells from apoptosis induced by androgen deprivation via the activation of Stat3/Bcl-2 pathway.
abstract: PrLZ/PC-1 is a newly identified, prostate-specific and androgen-inducible gene. Our previous study showed that PrLZ can enhance the proliferation and invasive capability of LNCaP cells, contributing to the development of prostate cancer. However, its potential role in androgen-independent processes remains elusive. In this study, we showed that PrLZ enhanced in vitro growth and colony formation of prostate cancer cells on androgen deprivation as well as tumorigenicity in castrated nude mice. In addition, PrLZ stabilized mitochondrial transmembrane potential, prevented release of cytochrome c from mitochondria to cytoplasm, and inhibited intrinsic apoptosis induced by androgen depletion. Mechanistically, PrLZ elevated the phosphorylation of Akt and Stat3 and upregulated Bcl-2 expression. Our data indicate that PrLZ protects prostate cancer cells from apoptosis and promotes tumor progression following androgen deprivation. In summary, we propose that PrLZ is a novel antiapoptotic gene that is specifically activated in prostate cancer cells escaping androgen deprivation may offer an appealing therapeutic target to prevent or treat advanced prostate malignancy.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.forename: Dalin
authors.initials: D
authors.lastname: He
authors.forename: Yan
authors.initials: Y
authors.lastname: Xue
authors.forename: Ruoxiang
authors.initials: R
authors.lastname: Wang
authors.forename: Kaijie
authors.initials: K
authors.lastname: Wu
authors.forename: Hongjun
authors.initials: H
authors.lastname: Xie
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.forename: Haiyen E
authors.initials: HE
authors.lastname: Zhau
authors.forename: Leland W K
authors.initials: LW
authors.lastname: Chung
authors.forename: Luke S
authors.initials: LS
authors.lastname: Chang
authors.forename: Lei
authors.initials: L
authors.lastname: Li
mesh_terms: D000728:Androgens / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002606:Charcoal / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D003911:Dextrans / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009025:Morpholines / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009919:Orchiectomy; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014183:Transplantation, Heterologous
chemical_list: D000728:Androgens; D002867:Chromones; D003911:Dextrans; D004791:Enzyme Inhibitors; D009025:Morpholines; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C114751:TPD52 protein, human; D002606:Charcoal; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt